Genome-wide CRISPR screen identifies AMBRA1 as a potential biomarker of response to platinum-based therapies in oral squamous cell carcinomas [CRISPR Screen]

Advanced stage tumors are still treated with standard chemotherapy, however, most of the patients develop chemotherapy resistance. To uncover new functional biomarkers of cisplatin response, we performed a synthetic lethality genome wide CRISPR/Cas9 screen in an oral squamous cell carcinoma cell line.

This led to the discovery of AMBRA1, as a regulator of cisplatin sensitivity. In all tested OSCC cell lines and oral primary cultures, AMBRA1 knockout cells showed increased sensitivity to cisplatin treatment. Mechanistically, we demonstrated a new function of AMBRA1, where loss of AMBRA1 led to higher S phase, higher expression of genome instability markers, and higher DNA damage in basal conditions, thereby predisposing cancer cells to an increased sensitivity to cisplatin as well as to other platinum drugs.